Parkinson’s Disease and the Gut Microbiome in Rural California

Article type: Research Article

Authors: Zhang, Keren^a | Paul, Kimberly C.^b | Jacobs, Jonathan P.^{a; c; d; e} | Chou, Hsiang-Chin (Lori)^a | Duarte Folle, Aline^a | Del Rosario, Irish^a | Yu, Yu^{f; g} | Bronstein, Jeff M.^b | Keener, Adrienne M.^b | Ritz, Beate^{a; b; f; *}

Affiliations: [a] Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA | [b] Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA | [c] Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, Los Angeles, CA, USA | [d] UCLA Microbiome Center, Los Angeles, CA, USA | [e] Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA | [f] Department of Environmental Health Science, UCLA Fielding School of Public Health, Los Angeles, CA, USA | [g] UCLA Center for Health Policy Research, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA

Correspondence: [*] Correspondence to: Professor Beate Ritz, MD, PhD, UCLA Fielding School of Public Health, 650 Charles E. Young Drive South, 73-320A Center for Health Sciences, Los Angeles, CA 90095, USA. Tel.: +1 310 206 7458; E-mail: britz@ucla.edu.

Abstract: Background: Increasing evidence connects the gut microbiome to Parkinson’s disease (PD) etiology, but little is known about microbial contributions to PD progression and its clinical features. Objective: We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. Methods: In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). Results: PD patients’ gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. Additionally, the postural instability gait dysfunction subtype was associated with three phyla and the NAD biosynthesis pathway. PD duration was associated with the Synergistota phylum, six genera, and the aromatic compound degradation pathways. Two genera were associated with motor function. Conclusion:PD patients differed from controls in gut microbiome composition and its predicted metagenome. Clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression.

Keywords: Parkinson’s disease, gut microbiome, brain-gut axis, Unified Parkinson’s Disease Rating Scale

DOI: 10.3233/JPD-223500

Journal: Journal of Parkinson's Disease, vol. 12, no. 8, pp. 2441-2452, 2022